Neuroscience
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Gonadectomy in adult male rats significantly impairs spatial working memory, behavioral flexibility and other functions associated with the prefrontal cortex (PFC). However, the mechanisms through which this occurs are largely unknown. In this study, intracortical drug challenge with the selective N-methyl-d-aspartate receptor (NMDAR) antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) was combined with Barnes maze testing, gonadectomy (GDX) and hormone replacement (17β-estradiol, testosterone propionate) to explore the contributions of NMDAR-mediated activity within the PFC to hormone effects on spatial cognition in adult male rats. ⋯ Together these findings suggest that hormone regulation of NMDAR-mediated activity specifically within the PFC may be fundamental to the effects of gonadal steroids on spatial cognition in males. Our findings further identify NMDAR antagonists as potentially novel, non-steroidal means of attenuating the cognitive deficits that can accompany gonadal hormone decline in human males in aging, clinical cases of hypogonadalism and in certain neurologic and psychiatric illnesses. Accordingly, it may be important to obtain in males the kind of detailed knowledge concerning hormone effects on, for example, the channel and electrophysiological properties of NMDAR that currently exists for the female brain.
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The myelin-associated protein Nogo-A is among the most potent neurite growth inhibitors in the adult CNS. Recently, Nogo-A expression was demonstrated in a number of neuronal subpopulations of the adult and developing CNS but at present, little is known about the expression of Nogo-A in the nigrostriatal system, a brain structure severely affected in Parkinson's disease (PD). The present study sought to characterize the expression pattern of Nogo-A immunoreactive (ir) cells in the adult ventral mesencephalon of control rats and in the 6-hydroxydopamine (6-OHDA) rat model of PD. ⋯ In the striatum, both small and large Nogo-A-positive cells were detected. The large cells were identified as cholinergic interneurons. Our results suggest yet unidentified functions of Nogo-A in the CNS beyond the inhibition of axonal regeneration and plasticity, and may indicate a role for Nogo-A in PD.
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The present study investigated the effects of chronic social defeat stress on several behavioral parameters, and the expression of dopaminergic markers, i.e., dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse brains. After 10days of social defeat stress, the defeated mice were divided into two groups: one group underwent a series of behavioral tests. The other group was sacrificed on the 11th day and tissue samples were collected for Western blotting. ⋯ No significant differences in D1Rs and D2Rs expression were shown between defeated and control mice in any area studied. A significantly increased expression in total DARPP-32, and phospho-DARPP-32 was observed in the PFC or AMY of defeated mice. These data suggest that alterations in dopaminergic markers may be involved in anxiety- and depression-like behaviors, and cognitive impairment induced by social defeat stress.
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The endocannabinoid system mainly consists of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), their endogenous ligands termed endocannabinoids (eCBs), and the enzymes responsible for the synthesis and degradation of eCBs. These cannabinoid receptors have been well characterized in rodent and monkey retinae. Here, we investigated the expression and localization of the eCB system beyond the retina, namely the first thalamic relay, the dorsal lateral geniculate nucleus (dLGN), of vervet monkeys using immunohistochemistry methods. ⋯ These proteins are weakly expressed in the koniocellular layers. These results suggest that the presence of the eCB system throughout the layers of the dLGN may represent a novel site of neuromodulatory action in normal vision. The larger amount of CB1R in the dLGN magnocellular layers may explain some of the behavioral effects of cannabinoids associated with the integrity of the dorsal visual pathway that plays a role in visual-spatial localization and motion perception.
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Comparative Study
GAD65/GAD67 double knockout mice exhibit intermediate severity in both cleft palate and omphalocele compared with GAD67 knockout and VGAT knockout mice.
Inhibitory neurotransmitters, γ-aminobutyric acid (GABA) and glycine, are transported into synaptic vesicles by the vesicular GABA transporter (VGAT). Glutamate decarboxylase (GAD) is a GABA-synthesizing enzyme and two isoforms of GAD, GAD65 and GAD67 are encoded by two independent genes. There was virtually no GABA content in GAD65/GAD67 double knockout (GADs DKO) mouse brains. ⋯ The severity of cleft palate and omphalocele was evaluated by elevation of palate shelves and size and liver inclusion of omphalocele, respectively. We observed that the phenotypes of cleft palate and omphalocele in GADs DKO mice were more and less severe than those in GAD67 KO and VGAT KO mice, respectively. These results indicate the significant contribution of not only GAD65-mediated GABAergic but also glycinergic transmissions to both palate and abdominal wall formations.